Systematic review and meta-analysis of the accuracy and applicability of blood-based multi-cancer early detection (MCED) in the general population.

person Joo Hee Park Northwestern University, Chicago, IL info_outline Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie Arni Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Young Kwang Chae

Authors person Joo Hee Park Northwestern University, Chicago, IL info_outline Joo Hee Park, Youjin Oh, Liam Il-Young Chung, Richard Duan, Trie Arni Djunadi, Sung Mi Yoon, Zunairah Shah, Chan Mi Jung, Ilene Hong, Leeseul Kim, Young Kwang Chae Organizations Northwestern University, Chicago, IL, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, Northwestern University Feinberg School of Medicine, Chicago, IL, Louis A Weiss Memorial Hospital, Chicago, IL, Northwestern University, Evanston, IL, Ascension Saint Francis Hospital, Evanston, IL Abstract Disclosures Research Funding No funding received None. Background: Globally, cancer results in 10.08 million deaths per year. A single blood-based screening tool that detects multiple cancer types could significantly reduce cancer burden. We systematically reviewed and statistically examined both the accuracy and applicability of blood-based MCED tests to strategize their utilization in improving cancer detection. Methods: Original articles were searched from PubMed, Cochrane, and Embase for blood-based screening tests analyzing multiple cancer types and asymptomatic human subjects. We excluded studies with small sample sizes (n<30), hypothesis-generating/diagnostic tests, and non-blood-based tests. For cfDNA-based assays, measurements of diagnostic accuracy were pooled for meta-analysis. Results: Of 1,074 records identified and screened, 15 case-control and 4 cohort studies were analyzed, most of which utilized cfDNA-based diagnostic tests. Twelve cfDNA studies selected for meta-analysis had pooled sensitivity of 0.623 (95%CI 0.517 - 0.719) and specificity of 0.975 (0.942 - 0.990). Summary ROC curve shows variability in sensitivity and specificity between studies. However, sensitivity and specificity were not affected by study type, gender, or assay type. Sensitivity was higher for advanced staged cancers (III/IV 0.774 (0.697 - 0.837)) than early-stage cancers (I/II 0.503 (0.366 - 0.639)). Among cancer types, no significant differences were detected. Lastly, false positive and false negative rates were 0.025 (0.010 - 0.058) and 0.447 (0.438 - 0.456), respectively. Conclusions: Given high sensitivities and specificities, MCED tests show promise as additional screening tools. However, in the general population, misdiagnosis burden from false positive and negative rates is anticipated. Although multiple barriers exist to their application in the clinic, MCED tests may improve patient outcomes for cancers with no conventional screening tools and provide additional credibility when combined with existing tools. Future prospective studies with large and diverse populations are warranted. Summarization of meta-analysis results on cfDNA-based multi cancer early detection tests. Sensitivity Specificity False Positive Rate False Negative Rate Events/Total 6414/11590 16093/16357 264/6678 5176/21269 Proportion (95% CI) 0.652 [0.537; 0.751] 0.978 [0.936; 0.992] 0.025 [0.010, 0.058] 0.447 [0.438; 0.456] 12 studies are included. CI = Confidence Interval.